Protective VEGF Inhibition for Isotoxic Dose Escalation in Glioblastoma (PRIDE)

May 15, 2026 updated by: University Hospital Tuebingen

A Phase IIa, Open-label, Multicenter Study of Radiochemotherapy With Isotoxic Dose Escalation and Protective VEGF Inhibition Using Bevacizumab in the Treatment of Patients With First Diagnosis of IDH Wild-type, MGMT Unmethylated Glioblastoma

Glioblastoma is the most aggressive brain tumor and often recurs locally despite intensive treatment. Standard chemoradiotherapy with 60 Gy may not be sufficient to control the tumor, and dose escalation seems to be warranted, but causes more toxicity. To address this, the multicentric PRIDE trial employs two cycles of bevacizumab to achieve dose escalation isotoxically. The goal is improved survival without significantly increasing side effects. The study uses a simultaneous integrated boost with a total dose of 75 Gy in 2.5 Gy per fraction.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

146

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Germany
      • Augsburg, Germany
        • Recruiting
        • Department of Radiation Oncology, University Hospital Augsburg
        • Contact:
      • Cologne, Germany
        • Recruiting
        • Department of Radiation Oncology, University Hospital Köln
        • Contact:
      • Frankfurt, Germany
        • Recruiting
        • Department of Radiation Oncology, University Hospital Frankfurt
        • Contact:
      • Freiburg im Breisgau, Germany
      • Leipzig, Germany
      • Mannheim, Germany
        • Recruiting
        • Department of Radiation Oncology, Medical Faculty Mannheim
        • Contact:
      • Munich, Germany
        • Recruiting
        • Department of Radiation Oncology, University Hospital, LMU Munich
        • Contact:
      • Regensburg, Germany
        • Recruiting
        • Department of Neurology, University Hospital Regensburg
        • Contact:
      • Tübingen, Germany, 72076

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • IDH wild-type, MGMT unmethylated glioblastoma patients
  • Informed consent
  • Age ≥18 and ≤70 years, smoking or non-smoking, of any ethnic origin
  • ECOG 0-2
  • Neutrophil counts >1500/µl, Platelet counts >100.000/µl, Hemoglobin > 8 g/dl, Serum creatinine <1.5-fold upper limit of normal (ULN), Bilirubin, AST or ALT <2.5-fold ULN unless attributed to anticonvulsants, Alkaline phosphatase <2.5-fold ULN
  • Adequate contraception
  • Serum creatinine ≤ 1.5 x ULN AND patients with urine dipstick for proteinuria < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should show urine protein to creatinine ratio ≤ 1

Exclusion Criteria:

  • Evidence of significant hemorrhage on postoperative MRI of the brain. Patients with asymptomatic, minor hemosiderin deposition, resolving postsurgical hemorrhagic changes, or punctate intratumoral hemorrhage (e.g., related to biopsy or surgery) are not excluded
  • Subjects on any drug suspected to interfere with bevacizumab at the time of study inclusion
  • Immuno-compromised patients, including known seropositivity for human immunodeficiency virus (HIV)
  • Known hypersensitivity to any component of the investigational drugs or excipients (allergy to or other intolerability of bevacizumab or excipients)
  • Any other significant medical illness or medically significant laboratory finding that would, in the investigator's judgement, make the patient inappropriate for this study, or would increase the risk associated with the patients' participation in the study
  • Incapability to undergo MRI
  • Prior treatment with bevacizumab for any indication
  • Contraindication and/or hypersensitivity to bevacizumab or its excipients. For details check the Summary of Product Characteristics Aybintio®
  • Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, III, IV), unstable angina pectoris, or myocardial infarction within 6 months prior to enrolment
  • Inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or >100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy
  • History of clinically significant cerebrovascular events within 6 months prior to enrolment. This includes ischemic stroke or transient ischemic attack. Small, clinically silent perioperative ischemic changes are not exclusionary.
  • Significant vascular disease (e.g. aortic aneurysm, aortic dissection or recent peripheral arterial thrombosis) within 6 months prior to enrolment
  • Evidence or history of recurrent thromboembolism (> 1 episode of deep venous thrombosis / peripheral embolism) during the past 2 years
  • Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
  • Chronic daily intake of aspirin > 325 mg/day or clopidogrel > 75 mg /day
  • History of intracranial abscess within 6 months prior to inclusion
  • History of abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment
  • History of ≥ grade 2 hemoptysis according to NCI-CTC criteria within 1 month prior to inclusion
  • Serious non-healing wound, ulcer or bone fracture

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 75 Gy with two cycles of bevacizumab
Radiation: Dose escalation of radiation dose beyond the therapeutic standard
Dose escalation to 75 Gy with concomitant radioprotectant bevacizumab
Other Names:
  • bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: Date of study inclusion (informed consent) to death or end of F/U
Overall Survival
Date of study inclusion (informed consent) to death or end of F/U

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability
Time Frame: Date of study inclusion (informed consent) to death or end of F/U
Safety and tolerability of dose escalation with bevacizumab according to CTCAE v5.0
Date of study inclusion (informed consent) to death or end of F/U
PFS-6
Time Frame: 6 months after the date of study inclusion (informed consent)
6 months rate of progression-free survival
6 months after the date of study inclusion (informed consent)
PFS
Time Frame: Date of study inclusion (informed consent) to death or progression
Progression-free survival
Date of study inclusion (informed consent) to death or progression
QoL
Time Frame: Date of study inclusion (informed consent) to death or end of F/U
Quality of life as determined by EORTC QLQ-C30/QLQ-BN 20
Date of study inclusion (informed consent) to death or end of F/U
Cognitive function
Time Frame: Date of study inclusion (informed consent) to death or end of F/U
Cognitive function determined by standard test batteries
Date of study inclusion (informed consent) to death or end of F/U
Exploratory objective
Time Frame: Date of study inclusion (informed consent) to death or end of F/U
Validation of prognostic 4-miRNA signature-based risk score
Date of study inclusion (informed consent) to death or end of F/U

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Tuebingen

Investigators

  • Principal Investigator: Maximilian Niyazi, Prof. Dr., University Hospital Tuebingen, Department of Radiation Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2024

Primary Completion (Estimated)

April 10, 2028

Study Completion (Estimated)

July 10, 2028

Study Registration Dates

First Submitted

April 30, 2023

First Submitted That Met QC Criteria

May 13, 2023

First Posted (Actual)

May 23, 2023

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 15, 2026

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-000565-32

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe